Cerebral vasodilators and cerebral excitometabolic agents up to the present time have been employed as therapeutical agents for the treatment of diseases such as dementia and amnesia. It has been reported that these agents are effective for the treatment of dementia caused by cerebrovascular disorders. However, these agents do not show a sufficient effect for the treatment of dementia due to causes other than cerebrovascular disorders.
Prolyl endopeptidase is well known as an enzyme which acts on biologically active peptides and substrates to cleave specifically the carboxyl site in proline moiety.
The prolyl endopeptidase decomposes vasopressin and thyrotropin releasing hormone which are closely related to a memory mechanism, and therefore, a relationship of the inhibitory effect of prolyl endopeptidase and amnesia has been the subject of long term studies. As a result, it is suggested that inhibitors for the prolyl endopeptidase are useful for the treatment of dementia and amnesia (Seikagaku Vol. 55, No. 8, page 831, 1983).
With regard to inhibitors of prolyl endopeptidase, Japanese patent application (OPI) No. 188317/85 (The term "OPI" as used herein refers to an unexamined Japanese patent application) discloses the compound represented by the formula: ##STR4##
With respect to thiazolidine compounds having structures related to the compounds of the present invention, several compounds have been reported in the literature. For example, the compound represented by the formula: ##STR5## is disclosed in Chemical Abstracts, Vol. 86, No. 17, 117082v (1977), and has been prepared to study fragments in Mass spectrum. The compound represented by the formula: is disclosed in Chemical Abstracts, Vol. 105, No. 25, 227322s (1986), and is an intermediate for the preparation of agents for treatment of liver disorders.
In Chemical Abstracts, Vol. 95, No. 19, 169173f (1981), Vol. 96, No. 15, 123303r (1982), the following thiazolidine compounds having hypotensive activities are disclosed: ##STR6##
However, it is not disclosed that those compounds have an inhibitory effect on prolyl endopeptidase, and that they are useful as therapeutical agents for the treatment of dementia and amnesia. Further, no thiazolidine compound of the present invention type structure as yet has been reported to have an inhibitory activity for prolyl endopeptidase enzyme.